Relapse remains the most persistent and significant problem in drug abuse treatment. As many as 90% of smokers who attempt to quit eventually relapse, and smokers remain at high risk for relapse well after their acute withdrawal symptoms have subsided. Although relapse most commonly occurs soon after abstinence, recent studies with animals indicate that drug-seeking responses to conditioned stimuli gradually increase in magnitude for as long as 6 months of abstinence, a phenomenon known as "incubation". While cue reactivity is closely linked to operant drug-seeking responses in the animal laboratory, the relationship between cue reactivity and drug-taking in humans has not been firmly established. We propose to investigate whether this incubation phenomenon occurs in human cigarette smokers by studying their reactivity to smoking cues and time to relapse to smoking after varying periods of abstinence and whether changes is cue reactivity are associated with changes in time to relapse. The project will be conducted at the University of Chicago, in parallel with a similar project at the National Institute on Drug Abuse Intramural Research Program in Baltimore. The goals of the study are: 1. To assess "incubation" of smoking-cue reactivity after increasing durations of abstinence in cigarette smokers. We will investigate the reactivity to smoking cues among abstinent cigarette smokers, as a function of duration of abstinence after 7, 14, and 35 days of abstinence. Based on the studies with laboratory animals, it is hypothesized that cue reactivity will be greater after longer periods of abstinence. 2. To assess "incubation" of the tendency to resume smoking after increasing durations of abstinence. After 7, 14 or 35 days of abstinence maintained with monetary incentives, subjects will be allowed to return to smoking, with gradually decreasing monetary incentives for maintaining abstinence. We tentatively hypothesize that the latency to smoking will decrease, and the likelihood of returning to smoking will increase, after longer periods of abstinence. This is a translational project that applies novel findings in laboratory animals to a clinical setting. The study uses an innovative procedure to investigate a phenomenon that has not yet been characterized in humans, but which may have clinical relevance for drug users attempting to abstain. The project is the result of a unique collaboration among basic and clinical scientists at the University of Chicago and the NIDA Intramural Research Program. [unreadable] [unreadable] [unreadable]